Carboxylic acids, esters inversion-esterification

The coupling of carboxylic acid 33 with alcohol 26 is performed using the Mitsunobu esterification conditions (DEAD, PPhs) to provide ester 34 with inversion of configuration at the newly formed stereogenic... 

A further useful preparative method of esterification is based on the reaction of carboxylic acids with acetals of A, A-dimethyl-formamide (21) [66]. The process occurs under mild conditions (1-2 hr, 20-80°) without acid or base catalyst and generally gives high yields (80-95%) of esters (methyl, ethyl, and benzyl). A two-step mechanism has been proposed (a, b—Fig, 5.10) and the second stage is envisaged as a normd Sn2 displacement proceeding with inversion at the alkyl carbon atom ( ). 

Ester Formation. A variety of alcohols react at room temperature with carboxylic acids in the presence of DEAD and TPP to produce the corresponding esters. When polyols are used, the reaction generally takes place at the less hindered hydroxyl group, as exemplified in the reaction of 1,3-butanediol (eq 3). When 1,2-propanediol or styrene glycol is used, however, the more sterically encumbered C-2 benzoate is predominantly obtained with complete inversion of the stereochemistry. This result has been explained by the formation of a dioxaphospholane (8) as the key intermediate (eq 4) 3b, i9,20a acyclic 1,4-diols such as isomaltitol, five-membered cyclic ether formation takes place in preference to esterification. 

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